Autocrine stimulation of AR4-2J rat pancreatic tumor cell growth by glycine-extended gastrin

Int J Cancer. 1996 May 29;66(5):653-8. doi: 10.1002/(SICI)1097-0215(19960529)66:5<653::AID-IJC12>3.0.CO;2-5.


Glycine-extended gastrin (gastrin-Gly) stimulates proliferation of AR4-2J pancreatic tumor cell line through a specific receptor, different from the gastrin-cholecystokinin B receptor. Our purpose was to determine whether AR4-2J cells produced gastrin-Gly and then whether the peptide was involved in an autocrine loop. First, proliferation of AR4-2J cells in serum-free medium was inhibited by a gastrin anti-sense oligodeoxynucleotide phosphorothioate and by antibodies specific for gastrin-Gly. In contrast, antibodies specific for alpha-amidated gastrin were without effect. By using RT-PCR, we have shown that AR4-2J cells expressed gastrin mRNA. The presence of gastrin-Gly, but not alpha-amidated gastrin, in serum-free media was detected by radioimmunoanalysis. Gel chromatography revealed that the predominant molecular forms secreted were glycine-extended gastrin-34 and gastrin- 17. Furthermore, epidermal growth factor (EGF), a stimulator of gastrin gene transcription, modulates gastrin-Gly secretion by AR4-2J. These data together suggest that gastrin-Gly is an autocrine growth factor for AR4-2J cells and that it participates with EGF in the regulation of AR4-2J-cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / pharmacology
  • Cell Division / drug effects
  • Cell Division / physiology
  • Epidermal Growth Factor / pharmacology
  • Gastrins / biosynthesis
  • Gastrins / metabolism
  • Gastrins / physiology*
  • Gene Expression
  • Humans
  • Molecular Sequence Data
  • Oligonucleotides, Antisense / pharmacology
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology*
  • Rats
  • Stimulation, Chemical
  • Thionucleotides / pharmacology
  • Tumor Cells, Cultured / drug effects


  • Antibodies
  • Gastrins
  • Oligonucleotides, Antisense
  • Thionucleotides
  • glycine-extended gastrin 17
  • Epidermal Growth Factor